Plasma amyloid beta X-42/X-40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease.

INTRODUCTION: Blood-based biomarkers are a cost-effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation-immunoassay (IP-IA) as a test for predicting cognitive decline. METHODS: We measured levels of amyloid beta (Aß)X-40 and AßX-42 in immunoprecipitated eluates from the DELCODE cohort. Receiver-operating characteristic (ROC) curves, regression analyses, and Cox proportional hazard regression models were constructed to predict AP by Aß42/40 classification in cerebrospinal fluid (CSF) and conversion to mild cognitive impairment (MCI) or dementia. RESULTS: We detected a significant correlation between AßX-42/X-40 in plasma and CSF (r = 0.473). Mixed-modeling analysis revealed a substantial prediction of AßX-42/X-40 with an area under the curve (AUC) of 0.81 for AP (sensitivity: 0.79, specificity: 0.74, positive predictive value [PPV]: 0.71, negative predictive value [NPV]: 0.81). In addition, lower AßX-42/X-40 ratios were associated with negative PACC5 slopes, suggesting cognitive decline. DISCUSSION: Our results suggest that assessing the plasma AßX-42/X-40 ratio via our semiautomated IP-IA is a promising biomarker when examining patients with early or preclinical AD. HIGHLIGHTS: New plasma Aß42/Aß40 measurement using immunoprecipitation-immunoassay Plasma Aß42/Aß40 associated with longitudinal cognitive decline Promising biomarker to detect subjective cognitive decline at-risk for brain amyloid positivity.

Symptomatic Clusters Related to Amyloid Positivity in Cognitively Unimpaired Individuals.

Background: The NIA-AA Research Framework on Alzheimer's disease (AD) proposes a transitional stage (stage 2) characterized by subtle cognitive decline, subjective cognitive decline (SCD) and mild neurobehavioral symptoms (NPS). Objective: To identify participant clusters based on stage 2 features and assess their association with amyloid positivity in cognitively unimpaired individuals. Methods: We included baseline data of N = 338 cognitively unimpaired participants from the DELCODE cohort with data on cerebrospinal fluid biomarkers for AD. Classification into the AD continuum (i.e., amyloid positivity, A+) was based on Aß42/40 status. Neuropsychological test data were used to assess subtle objective cognitive dysfunction (OBJ), the subjective cognitive decline interview (SCD-I) was used to detect SCD, and the Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPS. A two-step cluster analysis was carried out and differences in AD biomarkers between clusters were analyzed. Results: We identified three distinct participant clusters based on presented symptoms. The highest rate of A+ participants (47.6%) was found in a cluster characterized by both OBJ and SCD. A cluster of participants that presented with SCD and NPS (A+:26.6%) and a cluster of participants with overall few symptoms (A+:19.7%) showed amyloid positivity in a range that was not higher than the expected A+ rate for the age group. Across the full sample, participants with a combination of SCD and OBJ in the memory domain showed a lower Aß42/ptau181 ratio compared to those with neither SCD nor OBJ. Conclusions: The cluster characterized by participants with OBJ and concomitant SCD was enriched for amyloid pathology.

Fornix fractional anisotropy mediates the association between Mediterranean diet adherence and memory four years later in older adults without dementia.

Here, we investigated whether fractional anisotropy (FA) of hippocampus-relevant white-matter tracts mediates the association between baseline Mediterranean diet adherence (MeDiAd) and verbal episodic memory over four years. Participants were healthy older adults with and without subjective cognitive decline and patients with amnestic mild cognitive impairment from the DELCODE cohort study (n = 376; age: 71.47 ± 6.09 years; 48.7 % female). MeDiAd and diffusion data were obtained at baseline. Verbal episodic memory was assessed at baseline and four yearly follow-ups. The associations between baseline MeDiAd and white matter, and verbal episodic memory's mean and rate of change over four years were tested with latent growth curve modeling. Baseline MeDiAd was associated with verbal episodic memory four years later (95 % confidence interval, CI [0.01, 0.32]) but not with its rate of change over this period. Baseline Fornix FA mediated - and, thus, explained - that association (95 % CI [0.002, 0.09]). Fornix FA may be an appropriate response biomarker of Mediterranean diet interventions on verbal memory in older adults.